Neuroimaging correlates of HIV-associated BBB compromise

The mechanisms underlying blood–brain barrier (BBB) compromise in human immunodeficiency virus (HIV) infection and the ways in which BBB compromise might impair neurocognitive function remain poorly understood. This study had two aims: (1) to examine the relationship between BBB breakdown, measured using contrast-enhanced magnetic resonance imaging (CE-MRI), plasma viral load, and neurological status; and (2) to examine the influence of highly active antiretroviral therapy (HAART) on the relationship between neuroinflammation using myoinositol/creatine (mI/Cr), a surrogate marker of glial activation as measured by magnetic resonance spectroscopy (MRS), and BBB compromise determined by CE-MRI. In 25 HIV-infected patients, we found that: (1) the severity of neurocognitive impairment correlated with the degree of BBB breakdown in the basal ganglia; (2) for any given degree of BBB compromise, patients with high plasma viral load were more severely impaired; (3) BBB compromise correlated with mI/Cr in the basal ganglia; and (4) for any given level of mI/Cr, the severity of BBB compromise and the severity of neurocognitive impairment were significantly less in patients on HAART than in those who were HAART-naïve. These results confirm a role for BBB compromise in the pathogenesis of HIV-associated neurocognitive impairment and suggest that elevated plasma viral load in the presence of BBB compromise may increase the risk for development of HIV-associated dementia (HAD). Additionally, they suggest a salutary effect of HAART on the incidence and severity of HAD, which may, in part, be due to protection of BBB integrity.